Investigational drugs for the treatment of osteoarthritis, an update on recent developments

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Abstract

<p class="first" id="d5285797e121">Osteoarthritis (OA) is the leading cause of pain, loss of function, and disability among elderly, with the knee the most affected joint. It is a heterogeneous condition characterized by complex and multifactorial etiologies which contribute to the broad variation in symptoms presentation and treatment responses that OA patients present. This poses a challenge for the development of effective treatment on OA. </p>

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Most cited references 175

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Osteoarthritis: a disease of the joint as an organ.

Richard F. Loeser, Steven R. Goldring, Carla R. Scanzello … (2012)

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The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis.

Jérémie Sellam, Francis Berenbaum (2010)

Osteoarthritis (OA), one of the most common rheumatic disorders, is characterized by cartilage breakdown and by synovial inflammation that is directly linked to clinical symptoms such as joint swelling, synovitis and inflammatory pain. The gold-standard method for detecting synovitis is histological analysis of samples obtained by biopsy, but the noninvasive imaging techniques MRI and ultrasonography might also perform well. The inflammation of the synovial membrane that occurs in both the early and late phases of OA is associated with alterations in the adjacent cartilage that are similar to those seen in rheumatoid arthritis. Catabolic and proinflammatory mediators such as cytokines, nitric oxide, prostaglandin E(2) and neuropeptides are produced by the inflamed synovium and alter the balance of cartilage matrix degradation and repair, leading to excess production of the proteolytic enzymes responsible for cartilage breakdown. Cartilage alteration in turn amplifies synovial inflammation, creating a vicious circle. As synovitis is associated with clinical symptoms and also reflects joint degradation in OA, synovium-targeted therapy could help alleviate the symptoms of the disease and perhaps also prevent structural progression.

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Inhibition of TGF–β signaling in subchondral bone mesenchymal stem cells attenuates osteoarthritis

Gehua Zhen, Chunyi Wen, Xiaofeng Jia … (2013)

Osteoarthritis is a highly prevalent and debilitating joint disorder. There is no effective medical therapy for osteoarthritis due to limited understanding of osteoarthritis pathogenesis. We show that TGF–β1 is activated in the subchondral bone in response to altered mechanical loading in an anterior cruciate ligament transection (ACLT) osteoarthritis mouse model. TGF–β1 concentrations also increased in human osteoarthritis subchondral bone. High concentrations of TGF–β1 induced formation of nestin+ mesenchymal stem cell (MSC) clusters leading to aberrant bone formation accompanied by increased angiogenesis. Transgenic expression of active TGF–β1 in osteoblastic cells induced osteoarthritis. Inhibition of TGF–β activity in subchondral bone attenuated degeneration of osteoarthritis articular cartilage. Notably, knockout of the TGF–β type II receptor (TβRII) in nestin+ MSCs reduced development of osteoarthritis in ACLT mice. Thus, high concentrations of active TGF–β1 in the subchondral bone initiated the pathological changes of osteoarthritis, inhibition of which could be a potential therapeutic approach.

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Author and article information

Contributors

Zhaohua Zhu: (View ORCID Profile)

Journal

Title: Expert Opinion on Investigational Drugs

Abbreviated Title: Expert Opinion on Investigational Drugs

Publisher: Informa UK Limited

ISSN (Print): 1354-3784

ISSN (Electronic): 1744-7658

Publication date Created: October 23 2018

Publication date Created: November 02 2018

Publication date (Electronic): October 24 2018

Publication date (Print): November 02 2018

Volume: 27

Issue: 11

Pages: 881-900

Affiliations

[1 ] Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, China

[2 ] Department of Rheumatology and Immunology, Arthritis Research Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, China

[3 ] Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia

[4 ] Department of Rheumatology & Immunology, Beijing Hospital, Beijing, China

Article

DOI: 10.1080/13543784.2018.1539075

PubMed ID: 30345826

SO-VID: fffbe4d9-54cf-4dac-9762-6ed4676b07eb

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Investigational drugs for the treatment of osteoarthritis, an update on recent developments

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Vector Biology

Most cited references 175

Osteoarthritis: a disease of the joint as an organ.

The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis.

Inhibition of TGF–β signaling in subchondral bone mesenchymal stem cells attenuates osteoarthritis

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